There is a demand for fluorinating agents which are site-selective towards organic, especially carbanionic, substrates, especially for use in the preparation of pharmacologically active compounds. A number of such electrophilic fluorinating agents are known but are limited in their commercial utility in that they are expensive, hazardous, inconvenient to handle, lack stability and/or are insufficiently selective for general use.
Fluorine (F.sub.2) solutions in halogenated or other suitable solvents at low temperature (about -78.degree. C.), trifluoromethyl hypofluorite (CF.sub.3 OF), caesium fluorosulphate (CsSO.sub.4 F) and perchloryl fluoride (FClO.sub.3) are all active electrophilic fluorinating agents (S. T. Purrington, et al., Chem. Rev., 1986, 86, 997 and G. G. Furin in "New Fluorinating Agents in Organic Synthesis", Ed. L. German and S. Zemskov, Springer-Verlag: Berlin, 1989, 35-68) but are either not sufficiently selective or too hazardous for general use. Xenon difluoride (XeF.sub.2) is potentially less hazardous but is too expensive in many applications.
Recently attention has been directed to the use of compounds of the N-F class, i.e. having an N-F bond, as electrophilic fluorinating agents. The prototypical member of this class is perfluoro-N-fluoropiperidine (R. E. Banks and G. E. Williamson, Chem. Ind. (London), 1964, 1864 and R. E. Banks et al, J. Chem. Soc., Perkin Trans. I, 1972, 1098). However, this compound is obtainable only in low yields by electrochemical fluorination of pyridine (about 8% yield) or 2-fluoropyridine (about 13% yield) in anhydrous hydrogen fluoride. Further, it has been found to be inadequately reactive in several applications and, on transfer of fluorine to a carbanionic substrate, liberates the imidoyl fluoride perfluoro-1-azacyclohex-1-ene which then competes for the substrate. Similar problems militate against use of the analogous compounds perfluoro-(N-fluoro-2,6-dimethylpiperidine) and perfluoro-N-fluoromorpholine (R. E. Banks et al, J. Chem. Soc., Perkin Trans. I, 1988, 2805) and of poly[perfluoro-(N-fluoropiperidin-4-ylethylene)] (R. E. Banks & E. Tsiliopoulos, J. Fluorine Chem., 1986, 34, 281) as electrophilic fluorinating agents.
Other members of the N-F class include N-fluoropyridin-2(1H)-one (S. T. Purrington and W. A. Jones, J. Org. Chem. 1983, 48, 761 and J. Fluorine Chem., 1984, 26, 43), N-fluoro-N-sulfonamides (U.S. Pat. Nos. 4479901, 4828764 and DE 3623184A) and N-fluoro-sultams (E. Differding and R. W. Lang, Tetrahedron Lett., 1988, 29, 6087).
More recently, interest in N-F class fluorinating agents has centered on N-fluoro quaternary nitrogen heterocyclic compounds, specifically N-fluoroquinuclidinium salts (R. E. Banks et al, J. Chem. Soc., Perkin Trans I, 1988, 2805 and R. E. Banks & I. Sharif, J. Fluorine Chem., 1988, 41, 297), N-fluoro-N-alkyl-2,2,6,6-tetramethylpiperidinium chlorate (I. V. Vigalok et al, J. Org. Chem. USSR, 1983, 19, 1203), and N-fluoropyridinium salts (Umemoto et al, Tetrahedron Lett., 1986, 27, 3271 & 4465 and T. Umemoto & G. Tomizawa, Bull. Chem. Soc. Jpn, 1986, 59, 3625).
The most attractive of these new fluorinating agents are the N-fluoropyridinium and, especially, N-fluoroquinuclidinium triflates (i.e. trifluoromethanesulfonates). Although pyridine is relatively cheap and readily available, quinuclidine is relatively expensive and in short supply. Further, because the hydrogen atoms at the 2 and 6 positions of N-fluoropyridinium compounds are quite acidic, difficulties arise when using the compounds with certain highly basic substrates (see T. Umemoto and G. Tomizawa, J. Org. Chem., 1989, 54, 1726).